Acetylator phenotyping by means of a sulphadimidine tests revealed 65% of Libyan Arabs to be slow acetylators. Hence the frequency of the allele controlling slow acetylation (As) is estimated as q = 0.81 +/- 0.05. This estimate is similar to those previously recorded in European and adjacent Middle Eastern populations.

https://jmg.bmj.com/content/jmedgenet/18/5/325.full.pdf

Human acetylator polymorphism: estimate of allele frequency in Libya and details of global distribution.

https://academiccommons.columbia.edu/doi/10.7916/D8CV4V8H/download

Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers.

Sulphamethazine, 8 mg/kg body weight, was administered orally in tablet form to 100 healthy volunteers and total and free sulphamethazine were determined in the six hour urine sample The bimodal population frequency distribution for percentage acetylated sulphamethazine showed 42 of the tested population to be fast and 58 to be slow acetylators, that is, an estimation of q = 072 +/- 03 as the frequency of the allele controlling slow acetylation The study also revealed ample evidence that the assay of the drug in urine can be done in a significantly shorter time

https://jmg.bmj.com/content/jmedgenet/25/1/29.full.pdf

Polymorphic acetylation of sulphamethazine in a Zimbabwe population.

The effect of acetaminophen on sulfamethazine N-acetylation by human N-acetyltrasferase-2 (NAT2) was studied in 19 (n=19) healthy male volunteers in two different phases. In the first phase of the study the volunteers were given an oral dose of sulfamethazine 500 mg alone and blood and urine samples were collected. After the 10-day washout period the same selected volunteers were again administered sulfamethazine 500 mg along with 1000 mg acetaminophen. The acetylation of sulfamethazine by human NAT2 in both phases with and without acetaminophen was determined by HPLC to establish their respective phenotypes. In conclusion obtained statistics of present study revealed that acetaminophen significantly (P<0.0001) decreased sulfamethazine acetylation in plasma of both slow and fast acetylator male volunteers. A highly significant (P<0.0001) decrease in plasma-free and total sulfamethazine concentration was also observed when acetaminophen was co-administered. Urine acetylation status in both phases of the study was found not to be in complete concordance with that of plasma. Acetaminophen significantly (P<0.0001) increased the acetyl, free and total sulfamethazine concentration in urine of both slow and fast acetylators. Urine acetylation analysis has not been found to be a suitable approach for phenotypic studies.

https://journals.sagepub.com/doi/pdf/10.1177/0394632015593238

Effect of acetaminophen on sulfamethazine acetylation in male volunteers

1. Sulphamethazine was administered orally to 165 Yoruba subjects (40 mg/kg body wt.). Free and acetylated sulphamethazine were determined in the 6h urines.2. The population frequency histogram for percentage of urinary acetylated sulphamethazine was bimodal, although not completely resolved. Slow acetylators constituted 45% of the population studied.3. This Yoruba population did not differ statistically (P>0.05) in this respect from the two major tribally distinct groups in Nigeria previously investigated.

Polymorphic acetylation of sulfamethazine in a Nigerian (Yoruba) population.

Sulfamethazine (syn. sulfadimidine) is inactivated by conversion to its N-acetyl derivative. Individuals are phenotyped as either “rapid” or “slow” acetylators. We have tested the validity of this theory in a Nigerian population. The frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum were found to be bimodal, indicating the existence of a genetic polymorphism as observed by earlier workers. A plot of the percentage of the drug acetylated in serum against that in urine of the same individual results in a satisfactory separation of the rapid and slow acetylator phenotypes. An incidence of the slow acetylator phenotype of 41% was observed in the Nigerian population tested. How this observation fits into the hypothesis that the slow frequency of the allele increases from the Arctic Circle toward the Equator is discussed.

O. Obidoa

Papers

Acetylation of sulfamethazine in a Nigerian population